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Cross-Ancestry DNA Methylation Marks of Insulin Resistance in Pregnancy : An Integrative Epigenome Wide Association Study

Fragoso-Bargas, N ; Elliott, H R ; Lee-Ødegård, S ; Opsahl, J O ; Sletner, L ; Jenum, A K ; Drevon, Christian A ; Qvigstad, E ; Moen, G-H and Birkeland, K I , et al. (2023) In Diabetes 72(3). p.415-426
Abstract

Although there are some epigenome-wide association studies (EWAS) of insulin resistance, most of them did not replicate their findings and are focused in populations of European ancestry limiting the generalizability. In EPIPREG (294 Europeans and 162 South Asians), we conducted an EWAS of insulin resistance in maternal peripheral blood leukocytes, with replication in Born in Bradford (n=879; 430 Europeans and 449 South Asians), MENA (n=320) and Botnia (n=56) cohorts. In EPIPREG, we identified six CpG sites inversely associated with insulin resistance across ancestry, whereof five were replicated in independent cohorts (cg02988288, cg19693031, and cg26974062 in TXNIP, cg06690548 in SLC7A11, cg04861640 in ZSCAN26). From methylation... (More)

Although there are some epigenome-wide association studies (EWAS) of insulin resistance, most of them did not replicate their findings and are focused in populations of European ancestry limiting the generalizability. In EPIPREG (294 Europeans and 162 South Asians), we conducted an EWAS of insulin resistance in maternal peripheral blood leukocytes, with replication in Born in Bradford (n=879; 430 Europeans and 449 South Asians), MENA (n=320) and Botnia (n=56) cohorts. In EPIPREG, we identified six CpG sites inversely associated with insulin resistance across ancestry, whereof five were replicated in independent cohorts (cg02988288, cg19693031, and cg26974062 in TXNIP, cg06690548 in SLC7A11, cg04861640 in ZSCAN26). From methylation quantitative trait loci analysis in EPIPREG, we identified gene variants related to all five replicated cross-ancestry CpG sites, which were associated with several cardiometabolic phenotypes. Mediation analyses suggested that the gene variants regulate insulin resistance through DNA methylation. To conclude, our cross-ancestry EWAS identified five CpG sites related with lower insulin resistance.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetes
volume
72
issue
3
pages
415 - 426
publisher
American Diabetes Association Inc.
external identifiers
  • scopus:85150066763
  • pmid:36534481
ISSN
1939-327X
DOI
10.2337/db22-0504
language
English
LU publication?
yes
additional info
© 2022 by the American Diabetes Association.
id
fafc6fd2-c458-4d51-a6ca-125fd15189d9
date added to LUP
2023-01-11 11:46:17
date last changed
2024-04-19 20:07:10
@article{fafc6fd2-c458-4d51-a6ca-125fd15189d9,
  abstract     = {{<p>Although there are some epigenome-wide association studies (EWAS) of insulin resistance, most of them did not replicate their findings and are focused in populations of European ancestry limiting the generalizability. In EPIPREG (294 Europeans and 162 South Asians), we conducted an EWAS of insulin resistance in maternal peripheral blood leukocytes, with replication in Born in Bradford (n=879; 430 Europeans and 449 South Asians), MENA (n=320) and Botnia (n=56) cohorts. In EPIPREG, we identified six CpG sites inversely associated with insulin resistance across ancestry, whereof five were replicated in independent cohorts (cg02988288, cg19693031, and cg26974062 in TXNIP, cg06690548 in SLC7A11, cg04861640 in ZSCAN26). From methylation quantitative trait loci analysis in EPIPREG, we identified gene variants related to all five replicated cross-ancestry CpG sites, which were associated with several cardiometabolic phenotypes. Mediation analyses suggested that the gene variants regulate insulin resistance through DNA methylation. To conclude, our cross-ancestry EWAS identified five CpG sites related with lower insulin resistance.</p>}},
  author       = {{Fragoso-Bargas, N and Elliott, H R and Lee-Ødegård, S and Opsahl, J O and Sletner, L and Jenum, A K and Drevon, Christian A and Qvigstad, E and Moen, G-H and Birkeland, K I and Prasad, R B and Sommer, C}},
  issn         = {{1939-327X}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{415--426}},
  publisher    = {{American Diabetes Association Inc.}},
  series       = {{Diabetes}},
  title        = {{Cross-Ancestry DNA Methylation Marks of Insulin Resistance in Pregnancy : An Integrative Epigenome Wide Association Study}},
  url          = {{http://dx.doi.org/10.2337/db22-0504}},
  doi          = {{10.2337/db22-0504}},
  volume       = {{72}},
  year         = {{2023}},
}